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Nat Cell Biol. 2015 Feb;17(2):170-82. doi: 10.1038/ncb3090. Epub 2015 Jan 12.

Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth.

Author information

  • 1Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
  • 2Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
  • 3Departments of Neurological Surgery &Pathology, University Hospitals, Case Medical Center &Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
  • 4Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

Tumour-associated macrophages (TAMs) are enriched in glioblastoma multiformes (GBMs) that contain glioma stem cells (GSCs) at the apex of their cellular hierarchy. The correlation between TAM density and glioma grade suggests a supportive role for TAMs in tumour progression. Here we interrogated the molecular link between GSCs and TAM recruitment in GBMs and demonstrated that GSCs secrete periostin (POSTN) to recruit TAMs. TAM density correlates with POSTN levels in human GBMs. Silencing POSTN in GSCs markedly reduced TAM density, inhibited tumour growth, and increased survival of mice bearing GSC-derived xenografts. We found that TAMs in GBMs are not brain-resident microglia, but mainly monocyte-derived macrophages from peripheral blood. Disrupting POSTN specifically attenuated the tumour-supportive M2 type of TAMs in xenografts. POSTN recruits TAMs through the integrin αvβ₃ as blocking this signalling by an RGD peptide inhibited TAM recruitment. Our findings highlight the possibility of improving GBM treatment by targeting POSTN-mediated TAM recruitment.

PMID:
25580734
PMCID:
PMC4312504
DOI:
10.1038/ncb3090
[PubMed - indexed for MEDLINE]
Free PMC Article
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